Latest documents http://publikationen.ub.uni-frankfurt.de/index/index/ Fri, 06 Jan 2012 09:50:21 +0200 Fri, 06 Jan 2012 09:50:21 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24995 Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder. Heike Weber; Claus Jürgen Scholz; Katharina Domschke; Christian Baumann; Benedikt Klauke; Christian P. Jacob; Wolfgang Maier; Jürgen Fritze; Borwin Bandelow; Peter Michael Zwanzger; Thomas Lang; Lydia Fehm; Andreas Ströhle; Alfons Hamm; Alexander L. Gerlach; Georg W. Alpers; Tilo Kircher; Hans-Ulrich Wittchen; Volker Arolt; Paul Pauli; Jürgen Deckert; Andreas Reif article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24995 Fri, 01 Jun 2012 09:50:21 +0200